Spectral-domain magnetomotive optical coherence tomography for in vivo molecular imaging of the eye Molecular in vivo imaging allows for diagnostic analysis, target screening, and therapeutic monitoring of disease at the molecular level. This can be achieved prior to evidence of anatomical changes that are detected with conventional imaging modalities. These methods of in vivo molecular imaging are currently utilized in several fields of medicine. Developed by Dr. Stephen A Boppart, magnetomotive optical coherence tomography (MMOCT) is a method for imaging the distribution of magnetic nano-particles that are coupled to specific proteins or cells within the tissues by applying an external dynamic magnetic field gradient during OCT scanning. The technique has been demonstrated successfully in a living tadpole by imaging the biodistribution of the magnetic nano-particles. This demonstration illustrates a powerful multi- modal platform for molecular imaging. However, no such method is available in the ophthalmic field Ophthalmology has a huge demand for in vivo imaging of the location of specific molecules or cells where in various mouse models there is a critical need for in vivo imaging of the location of specific molecules or cells for studying a wide range of ocular diseases. One of such application is the dynamic tracking of selected proteins during the development of glaucoma, like that which occurs in a mouse model of this disease. Proteins such as cochlin and exon-trapped X chromosome clone 1 (ETX1) have been confirmed to be elevated in glaucomatous DBA/2J mouse model by immunohistochemistry. We have successfully developed our own ultra-high resolution OCT specifically for imaging the anterior segment of the eye. As shown in the preliminary results, with the incorporation of a magnetic coil and drive electronics, we have also built a prototype of the MMOCT and the in vivo magnetic response has been successfully detected. We propose to further develop and optimize the MMOCT with ultra-high speed and ultra-high resolution to image magnetic particle-coupled molecules in living mice (SA 1). After we have fully optimized the system and developed suitable magnetic nano-particles, we will test the hypothesis that magnetic nano-particle- coupled antibodies will enable dynamic detection and localization of antigens in the trabecular meshwork in an animal model of glaucoma (SA 2). This highly exploratory and innovative approach to imaging molecules in the eyes using MMOCT will tremendously widen the research applications of the OCT technique and significantly advance our capability to study ocular diseases. Additionally, it will provide insight into the process of normal aging at the molecular level. Development of this novel technology will have an extremely high impact on further studies. For instance, it will enable detection of correlations among specific proteins with normal aging and diseased stages. The method can be expanded further in imaging the posterior segment of the eye using a posterior segment scanning probe. Fundamentally, the MMOCT will lead to the development of new approaches to the diagnosis and treatment of abnormalities of the eye. PUBLIC HEALTH RELEVANCE: Molecular in vivo imaging allows for diagnostic imaging, target screening, and therapeutic monitoring of disease on a molecular level, prior to evidence of anatomical changes that are detected with conventional imaging modalities. We propose to further develop and optimize a magnetomotive optical coherence tomography (MMOCT) with an ultra-high speed and ultra-high resolution for imaging magnetic particle coupled molecules in living mouse models.